美托洛尔EP杂质N

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° C. overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6-oxo-5-bromo-4,5,6,7-tetrahydrobenzothiazole (100 parts), 3-isopropylamino-1,2-propanediol (67 parts), p-toluenesulfonic acid monohydrate (99 parts) and toluene (1550 parts) is heated under reflux for 21 hours while drying the refluxing azeotropic mixture according to the method described in Example I. After cooling, the reaction mixture is adjusted to pH 9 by adding aqueous 2.5N-sodium hydroxide and formed organic layer is separated. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts), and stirred for 49 hours on an oil bath heated at 95° to 100° C. The reaction mixture is concentrated under reduced pressure to leave residue which is mixed with ethyl acetate and water, shaken and fractionated to separate formed organic layer. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Residue (172 parts) is recrystallized from ethanol-hydrochloric acid giving 6-(3-isopropylamino-2-hydroxypropoxy)benzothiazole) (65 parts) in 57% yield. mp. 132°-134° C. (hydrochloride trihydrate). is heated under reflux for 21 hours while drying the refluxing azeotropic mixture After cooling by adding aqueous 2.5N-sodium hydroxide formed organic layer is separated The organic layer is washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure The remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts) heated at 95° to 100° C The reaction mixture is concentrated under reduced pressure to leave residue which shaken to separate formed organic layer The organic layer is washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure Residue (172 parts) is recrystallized from ethanol-hydrochloric acid

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° C. overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6-oxo-5-bromo-4,5,6,7-tetrahydrobenzothiazole (100 parts), 3-isopropylamino-1,2-propanediol (67 parts), p-toluenesulfonic acid monohydrate (99 parts) and toluene (1550 parts) is heated under reflux for 21 hours while drying the refluxing azeotropic mixture according to the method described in Example I. After cooling, the reaction mixture is adjusted to pH 9 by adding aqueous 2.5N-sodium hydroxide and formed organic layer is separated. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts), and stirred for 49 hours on an oil bath heated at 95° to 100° C. The reaction mixture is concentrated under reduced pressure to leave residue which is mixed with ethyl acetate and water, shaken and fractionated to separate formed organic layer. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Residue (172 parts) is recrystallized from ethanol-hydrochloric acid giving 6-(3-isopropylamino-2-hydroxypropoxy)benzothiazole (65 parts) in 57% yield. mp. 132°-134° C. (hydrochloride trihydrate). is heated under reflux for 21 hours while drying the refluxing azeotropic mixture After cooling by adding aqueous 2.5N-sodium hydroxide formed organic layer is separated The organic layer is washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure The remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts) heated at 95° to 100° C The reaction mixture is concentrated under reduced pressure to leave residue which shaken to separate formed organic layer The organic layer is washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure Residue (172 parts) is recrystallized from ethanol-hydrochloric acid

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° C. overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 37 g (0.5 mole) of glycidol and 35.4 g (0.6 mole) of isopropylamine was stirred at 25° overnight. Excess isopropylamine was evaporated in vacuo and the mixture was distilled to give 53 g of product: b.p. 80° C./0.1 mm Hg. The NMR and IR spectra were consistent with the assigned structure and the elemental analysis was consistent with the empirical formula C6H15O2N. Excess isopropylamine was evaporated in vacuo the mixture was distilled